| Autor: |
Sol, Olivier, Lê, Bénédicte, Wagg, Jonathan, Delpretti, Saskia, Fiorini, Emma, Vukicevic, Marija, MacSweeney, Emer, Borejko, Olga, Aarsland, Dag, Arús, Xavier Morató, Boada, Mercè, Matias‐Guiu, Jordi A, Lleo, Alberto, Fournier, Nicolas, Valatsou, Elena, Feige, Agnès, Rongere, Julien, Gray, Julian JG, Hliva, Valerie, Fortea, Juan |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 21, Vol. 19 Issue 21, p1-2, 2p |
| Abstrakt: |
Background: Sporadic Alzheimer's disease (AD) and Down syndrome related AD (DSAD) share a common neuropathologic picture, with hallmark amyloid plaques and neurofibrillary tangles. The key constituents, amyloid beta (Abeta) and tau, respectively, define the biomarker picture shared between sporadic AD, DSAD and autosomal dominant AD. Small Abeta oligomers and fragments such as Abeta 1‐42 and pyroglutamate Abeta3‐42 (pGlu‐Abeta3‐42) are key for disease initiation and neurotoxicity. ACI‐24 is a liposomal vaccine targeting Abeta. Initial clinical data demonstrated safety and pharmacodynamic response, both in sporadic AD and people with DS. Preclinical data recently demonstrated that a new, optimized formulation of ACI‐24 (ACI‐24.060) has significantly improved immunogenicity against key toxic species, i.e., Abeta oligomers, Abeta 1‐42 and pGlu‐Abeta3‐42. Method: Recent clinical trials evaluating monoclonal antibodies targeting Abeta in AD have successfully employed translational biomarkers, including amyloid PET, as surrogate markers to predict clinical benefit. These biomarkers can now be more effectively used in clinical trials for both patient selection and demonstrating treatment efficacy. Result: The ABATE study's (NCT05462106) innovative translational clinical trial design evaluates the effects of ACI‐24.060 in sporadic AD (Part 1) and in people with DS (Part2). The biomarker‐based design with multiple interim analyses, enables (I) early assessment of safety and immunogenicity, (II) appropriate dose selection using readouts on translational biomarkers including amyloid PET, (III) the safe transition into the DS population and (IV) informed transition into pivotal studies. The use of these shared biomarkers in predictable and pre‐specified trajectories allows effective cross‐learnings between sporadic AD and DSAD and has been enabled by the recent results with anti‐Abeta monoclonal antibodies, strongly enabling this translational approach for an amyloid immunotherapy. Initial safety and immunogenicity data will be presented. Conclusion: The field of biomarker‐based translational medicine has been mobilized by the clinical evaluation of targeting of toxic abeta fragments and aggregates in monoclonal antibody trials. As shown we are utilizing these advances in an innovative clinical trial design for an efficient, evidence‐based translational medicine approach to test ACI‐24.060 as a novel Abeta vaccine candidate. This approach allows the parallel investigation of ACI‐24.060 for the treatment and prevention of both sporadic AD and DSAD. [ABSTRACT FROM AUTHOR] |
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